The invention relates to methods for co-cultivating cells in micropatterned formations (e.g., for the production of bioartificial organs).
Co-cultures of hepatocytes with another cell type have been recognized to prolong cell survival rates, maintain phenotype, and induce albumin secretion in hepatocytes. Such co-cultures have been limited by the inability to manipulate or control the interaction of the two cell types in the culture. Generally, to prepare conventional co-cultures, cells of one type are seeded onto a substrate and allowed to attach; cells of a second type then are seeded on top of the cells of the first type. In such co-cultures, parameters such as cell number are controllable, but the spatial orientation of cells within the co-culture is not controlled (Element, B., et al. "Long-Term Co-Culture of Adult Human Hepatocytes with Rat Liver Epithelial Cells: Modulation of Albumin Secretion and Accumulation of Extracellular Material" Hepatology 4(3): 373-380 (1984); Schrode, W., et al. "Induction of Glutamine Synthetase in Periportal Hepatocytes by Cocultivation with a Liver Epithelial Cell Line" Euro. J. Cell Biol. 53: 35-41 (1990); Michalopoulos, G., et al., In Vitro 15(10): 796-806 (1979); Guguen-Guillouzo, C., et al. "Maintenance and Reversibility of Active Albumin Secretion by Adult Rat Hepatocytes Co-Cultured with Another Liver Epithelial Cell Type" Experimental Cell Research 143: 47-54 (1983); Begue, J. et al. "Prolonged Maintenance of Active Cytochrome P-450 in Adult Rat Hepatocytes Co-Cultured with Another Liver Cell Type" Hepatology 4(5): 839-842 (1984); Agius, L. "Metabolic Interactions of Parenchymal Hepatocytes and Dividing Epithelial Cells in Co-culture" Biochem. J. 252: 23-28 (1988); and Reid, L. et al. "Culturing Hepatocytes and Other Differentiated Cells" Hepatology 4(3): 548-559 (1984)).